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Modulation of Second Messengers in the Nervous System of Larval Manduca sexta by Muscarinic Receptors
Author(s) -
Trimmer Barry A.,
Qazi Sanjive
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66051903.x
Subject(s) - oxotremorine , muscarinic acetylcholine receptor , muscarinic agonist , endocrinology , medicine , inositol , inositol phosphate , biology , second messenger system , acetylcholine , muscarinic acetylcholine receptor m1 , muscarinic acetylcholine receptor m3 , agonist , chemistry , receptor , biochemistry
Measurements were made of the effects of muscarinic agents on endogenous levels of cyclic AMP and cyclic GMP, and the turnover of radiolabeled inositol phosphates in the abdominal nervous system of larval Manduca sexta . Cyclic AMP levels were increased by treatment with 3‐isobutyl‐1‐methylxanthine or tetrodotoxin, but the muscarinic agonist oxotremorine‐M and the muscarinic antagonist scopolamine had no consistent effects. In contrast, cyclic GMP levels were significantly increased by oxotremorine‐M and by oxotremorine‐M in the presence of 3‐isobutyl‐1‐methylxanthine and tetrodotoxin but not in the presence of scopolamine. Using lithium to inhibit the recycling of inositol phospholipid metabolites in isolated nerve cords, we detected a small but consistent increase in inositol phosphate production by oxotremorine‐M. The primary inositol metabolite generated during a 5‐min exposure to oxotremorine‐M co‐eluted from ion‐exchange columns with inositol‐1‐monophosphate, although other more polar metabolites were also detected. This agonist‐evoked increase in inositol phosphate production was unaffected by tetrodotoxin but inhibited by scopolamine, suggesting that it is directly mediated by muscarinic receptors. Further evidence for coupling between muscarinic receptors and inositol metabolism was obtained using a cell‐free preparation of nerve cord membranes labeled with [ 3 H]inositol. Incubation with oxotremorine‐M evoked a significant increase in labeled inositol bisphosphate, consistent with muscarinic receptors coupling to phosphatidylinositol metabolism. The accumulation of inositol bisphosphate in cell‐free preparations suggests that the normal breakdown to inositol monophosphate requires cytosolic components. Together, these results indicate that muscarinic acetylcholine receptors in Manduca couple predominantly to the inositol phospholipid signaling system, although some receptors may modulate cyclic GMP.